The insecticide β-Cyfluthrin induces acute arrhythmic cardiotoxicity through interaction with NaV1.5 and ranolazine reverses the phenotype

3-Cyfluthrin, a class II Pyrethroid, is an insecticide used worldwide in agriculture, horticulture (field and protected crops), viticulture, and domestic applications. 3-Cyfluthrin may impair the function of biological systems; however, little information is available about its poten-tial cardiotoxic effect. Here, we explored the acute toxicity of 3-Cyfluthrin in isolated heart preparations and its cellular basis, using isolated cardiomyocytes. Moreover, 3-Cyfluthrin effects on the sodium current, especially late sodium current (INa-L), were investigated us-ing human embryonic kidney cells (HEK-293) cells transiently expressing human NaV1.5 channels. We report that 3-Cyfluthrin raised INa-L in a dose-dependent manner. 3-Cyfluthrin prolonged the repolarization of the action potential (AP) and triggered oscillations on its duration. Cardiomyocytes contraction and calcium dynamics were disrupted by the pesti-cide with a marked incidence of non-electronic-stimulated contractions. The antiarrhyth-mic drug Ranolazine was able to reverse most of the phenotypes observed in isolated cells. Lastly, ventricular premature beats (VPBs) and long QT intervals were found during 3-Cyfluthrin exposure, and Ranolazine was able to attenuate them. Overall, we demon-strated that 3-Cyfluthrin can cause significant cardiac alterations and Ranolazine ame-liorated the phenotype. Understanding the insecticides' impacts upon electromechanical properties of the heart is important for the development of therapeutic approaches to treat cases of pesticides intoxication.

Automated summary

This study investigated the acute toxicity of 3-Cyfluthrin on the heart and its cellular basis. The results showed that 3-Cyfluthrin caused significant cardiac alterations, including prolongation of the action potential repolarization and disruption of cardiomyocyte contraction and calcium dynamics. The antiarrhythmic drug Ranolazine was able to attenuate these alterations.